This project is a continuation of a Project of the current Program Project and is concerned with the role of the dorsal column (DC) in transmitting visceral nociceptive signals to the brain. Hypothesis 1 is that the DC is the main pathway for nociceptive transmission from the genitourinary system, as well as from the gastrointestinal system. The behavioral responses to inflammation of the colon or of the urinary bladder will be compared before and after an upper cervical lesion of the DC, and electrophysiological responses of thalamic neurons will be recorded before and after a lesion of the DC or of the spinothalamic tract (STT). Hypothesis 2 is that visceral inflammation will sensitize primary visceral afferents and also postsynaptic dorsal column (PSDC) and STT neurons. The responses of visceral primary afferents and central neurons will be observed before and after inflammation of the colon, ureter or urinary bladder. Hypothesis 3 is that somewhat different cellular mechanisms underlie central sensitization of visceral responses following visceral inflammation, depending on the cause of the inflammation. There may also be different mechanisms of visceral and somatic responses. The experiments will involve immunostaining of PSDC and STT cells for neuropeptide receptors, behavioral studies or the effects of peptide receptor antagonists, electrophysiological investigations of the action of neurotransmitter receptor agonists and antagonists, and patch-clamp recordings from neurons in spinal cord slices. Hypothesis 4 is that nociceptive signals in the DC activate descending facilitatory pathways that enhance the responses of PSDC and STT neurons and that the facilitatory pathways involve the cerebellum. Studies will be made to confirm the importance of descending facilitation and that cerebellar cortical stimulation can enhance visceral responses.